• Safety, tolerability and pharmacokinetics of orally administered PXD101 for each cohort.
• Establish an MTD for once daily dosing and twice daily dosing in patients with advanced solid tumors, by study end.

• Determine the pharmacokinetics of oral PXD101 when dosed once or twice daily at various dose levels [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
• Explore anti-tumor activity [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
• Determine the safety, tolerability, and anti-tumor activity of orally administered PXD101 to patients with lymphoma [ Time Frame: throughout the trial ] [ Designated as safety issue: Yes ]

• Determine the pharmacokinetics of oral PXD101 when dosed once or twice daily at various dose levels.
• Explore anti-tumor activity, by study end.

This is a Phase I dose escalation study of PXD101 administered orally. Oral belinostat will be given once or twice daily at various dosing schedules to patients with solid tumors. Doses will be escalated until the maximum tolerated dose (MTD) is identified. In parallel, a cohort of lymphoma patients will be given oral belinostat on a discontinuous once daily dosing schedule.

• Solid Tumor
• Lymphoma

Inclusion Criteria:

• Age ≥ 18 years
• Solid tumor: Histologically confirmed solid tumors.
• Lymphoma: relapsed or refractory B-cell or T-cell lymphoma, NK-cell lymphoma or Hodgkins disease
• At least one evaluable lesion. Lesions must be evaluated by computed tomography (CT), magnetic resonance imaging (MRI), or bone scan. Patients with prostate cancer, bone disease and rising prostate-specific antigen [PSA] but no other evaluable disease are eligible and will be evaluated based on PSA. For lymphoma patients, lesions can also be measured by PET and/or evaluated in peripheral blood or bone marrow.
• Progressive disease: Progressive disease will be defined as new or progressive lesions on CT-scan, MRI, bone scan or by rising PSA
• ≥ 4 weeks since prior radiation therapy or chemotherapy
• Karnofsky performance ≥ 60%

• Solid Tumor: Acceptable liver, renal and bone marrow function to include:

  • absolute neutrophil count ≥ 1.5 x 10^9/L
  • hemoglobin ≥ 9.0 g/dl
  • platelets ≥ 100 x 10^9/L
  • bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • AST and ALT ≤ 3.0 x ULN (≤ 5.0 x ULN is acceptable if liver has tumor involvement)
  • serum creatinine ≤ 1.5 x ULN
  • PT-INR/PTT ≤ 1.5 x ULN, or for patients on anticoagulation therapy, status within therapeutic range

• Lymphoma: Acceptable liver, renal and bone marrow function including the following:

  • absolute neutrophil count ≥ 1.0 x 10^9/L
  • platelets ≥ 50 x 10^9/L
  • bilirubin ≤ 1.5 x upper limit of normal (ULN), or ≤3 times ULN if documented hepatic involvement with lymphoma, or ≤5 times ULN if history of Gilbert's disease
  • AST and ALT ≤ 3.0 x ULN (≤ 5.0 x ULN is acceptable if liver has tumor involvement)
  • serum creatinine ≤ 1.5 x ULN
  • PT-INR/PTT ≤ 1.5 x ULN, or in the therapeutic range if on anticoagulation therapy
• Serum potassium within normal range
• Estimated life expectancy of greater than 3 months
• Signed informed consent prior to any study specific procedures

Exclusion Criteria:

• Prior treatment with PXD101

• Within 4 weeks of enrollment:

  • major surgery
  • metastatic disease requiring palliative treatment

  • Anticancer therapy, including:

    • chemotherapy
    • radiotherapy
    • endocrine therapy
    • immunotherapy
    • other investigational agents (6 weeks for mitomycin or nitrosourea)
    • Lymphoma patients: No anticancer therapy within 2 weeks except for Rituximab which patients should be off for greater than 3 months unless there is evidence of disease progression.
• Serious concomitant systemic disorders (eg, active infection) compromising patient safety.
• Symptomatic brain metastases

• Significant cardiovascular disease, including:

  • unstable angina pectoris
  • uncontrolled hypertension
  • congestive heart failure (New York Heart Association [NYHA] Class III or IV) related to primary cardiac disease, a condition requiring anti-arrhythmic therapy
  • ischemic or severe valvular heart disease
  • myocardial infarction within 6 months prior to the trial entry

• A marked baseline prolongation of QT/QTc interval, such as:

  • repeated demonstration of a QTc interval > 500 msec
  • Long QT syndrome
  • required use of concomitant medication on dosing days that may cause torsade de pointes
• Altered mental status precluding understanding of the informed consent process and/or completion of the study
• Pregnant or breast-feeding women
• Refusal or inability to use effective means of contraception (for men and women of childbearing potential)
• History of, or test positive for, HIV.
• Lymphoma patients who have relapsed within 100 days of autologous or allogenic transplantation.